Method for controlling pests



United States Patent 3,260,588 METHOD FOR CONTROLLING PESTS HansjuergenA. Schroeder, New Haven, Conn., assignor to Olin Mathieson ChemicalCorporation, a corporation of Virginia No Drawing. Original applicationMar. 15, 1961, Ser. No. 95,829. Divided and this application July 1,1963, Ser. No. 296,882

9 Claims. (Cl. 71-25) This application is a division of co-pendingapplication, Serial No. 95,829, filed March 15, 1961.

This invention relates to a method of controlling soil fungi,nematodesyand other pests using certain3-trichloromethyl-S-Substituted-1,2,4-thiadiazoles having the formula inwhich X is selected from the group consisting of Cl, NH NHR, NR OR andSR where R is an alkyl group of 1 to 4 carbon atoms. This invention alsorelates to these compounds as novel compositions of matter.

These novel 3-trichloromethyl 5 substituted-1,2,4-thiadiazoles areoutstandingly effective soil fungicides. Compounds of this group, whenmixed into the soil, protect seeds and growing plants against anunusually broad spectrum of important pathogenic fungi, like species ofPythium, Fusarium, Rhizoctonia and Sclerotium. The activity against suchfungi is generally superior to the best available fungicides in useagainst these pathogens. This broad spectrum of effectiveness is rareand contributes great economic potential to this invention. Furthermore,when applied to soil even at rates much higher than required for diseasecontrol, no injury occurred to seeded crops. Thus, cotton, corn,cucumber, pea and bean grow normally in soil containing 50 p.p.m. of achemical of this group. Another advantage is the ability of preferredexamples of this invention to control seedling diseases when thechemical is mixed only into the soil used to cover the seeds. A furtheradvantage is the resistance of these compounds to removal from soil byrainfall leaching. Four inches of water did not appreciably reduce thecontrol of the Pythium disease of cotton in one test of a member of thisnovel group of compounds. Still another advantage is the resistance ofthese compounds to microbiological degradation and physical inactivationin soil. Soil treated with 50 p.p.m. of one of these novel compounds andheld for 30 days before planting still showed 100 percent control of thePythium disease of cotton.

In addition to the above mentioned soil fungicide activity, compounds ofthis invention exhibit further utility in three other pesticidal areas:(1) for the control of nematodes attacking the roots of plants, (2) forthe control of undesirable vegetation by applications to growing plants,(3) for the control of foilage diseases. Illustrations of such utilityare given in examples of specific compounds which follow.

The novel 5-chloro compound is prepared by a novel procedure of reactingtrichloromethylacetamidine or its hydrochloride withtrichloromethanesulfenyl chloride in the presence of alkali.Advantageously and preferably the reaction is carried out in thepresence of aqueous alkali and an inert immiscible organic solvent.Methylene chloride is preferred as the organic solvent but other inerthalogenated or non-halogenated solvents may be used, for example,chloroform, carbon tetrachloride, ethylene dichloride,trichloroethylene, benzene, toluene and cyclohexane. The reactionproceeds rapidly at low F 4 3,260,588 Ce Patented July 12, 1966temperatures, for example, 5 to +5 C., although higher or lowertemperatures may be employed. The product is recovered from the organicsolvent by any suitable means, for example, distillation.

The novel 5-chloro compound is a liquid having a refractive index at 21C. of 1.572 and a boiling point of about 225 C. at atmospheric pressure.It is soluble in acetone, ether, petroleum ether and carbontetrachloride.

The novel S-ethoxy-compound is prepared from the 5- chloro compound bytreatment with an alkali metal ethylate, conveniently prepared bydissolving the alkali metal in an excess of ethanol. The sodium,potassium or other alkali metal ethylate prepared in any otherconventional manner is suitable. The reaction of the chloro compoundwith theethylate proceeds rapidly at room temperature. By-product sodiumchloride is removed and the product is recovered from solution, forexample, by distillation.

The novel 5-ethoxy compound is a liquid having a refractive index at 30C. of 1.5355 and a boiling point of C. at 1 mm. Hg pressure. It issoluble in acetone, ether, petroleum ether and carbon tetrachloride.

The novel S-methoxy and 5-but0xy compounds are prepared from theappropriate alkali metal alcoholates analogously to the ethoxy compound.The novel amino compounds are prepared from the 5-chloro compound by theaction of ammonia or amines, for example, methylamine, diethylamine, orisopropylamine, advantageously dissolved in alcohol solution. Species ofthe compounds of this invention also include:

3-trichloromethyl-5-methylamino-1,2,4-thiadiazole3-trichloromethyl-S-dimethylamino-1,2,4-thiadiazole3-trichloromethyl-S-isopropylamino-1,2,4-thiadiazole3-trichloromethyl-5isopropoxy-1,2,4-thiadiazole3-trichloromethyl-S-isobutylthio-1,2,4-thiadiazole3-trichloromethyl-5-ethylthio-1,2,4-thiadiazole In small scale tests,these soil fungicides are effective in proportions of from about 5 toabout parts per million of soil. In larger scale operations, quantitiesof from 2 to 20 pounds or more per acre are suitable.

Example 1 A solution of 65 grams (1.625 moles) of sodium hydroxide inmilliliters of water was added dropwise with stirring during 2 hours toa mixture of 75 grams (0.378 mole) of trichloroacetamidinehydrochloride, 70 grams (0.376 mole) of trichloromethanesulfenylchloride and 500 milliliters of methylene chloride. The temperature waskept between 4 C. and 1 C. by cooling in an ice-salt mixture. Themethylene chloride layer was separated, washed twice with 50 millilitersof water and dried with sodium sulfate. After evaporation of thesolvent, the residue was vacuum distilled to obtain 50 grams (56 percentof the theoretical yield) of3-trichloromethyl-S-chloro-1,2,4-thiadiazole. I-t boiled at 73 C. at 0.3mm. Hg pressure and had N =1.5720.

Analysis.Calc. for C Cl N S: C, 15.14; Cl, 59.61; N, 11.77; S, 13.47.Found: C, 15.25; Cl, 59.65; N, 11.91; S, 13.21.

The compounds of this invention were tested as a soil fungicide by themethod of J. H. Reinhart entitled, A method of evaluating fungicides inthe soil under controlled conditions, which appeared in Plant DiseaseReporter, 442648-652, 1960. Briefly, the method consists of preparingthe chemicals as a 10 percent dust, thoroughly blending with 90 percentof a mixture of Pyrax and Microcel (8:1). (Pyrax is a finely powderedaluminum silicate of the pyrophyllite type. Microcel is an adsorptive,synthetic calcium silicate.) The 10 percent dust is mixed into soilwhich has been infested with a pure culture of the fungus pathogen, andalso seeded with a crop susceptible to the disease. The number ofhealthy plants obtained from the treated soils compared to those inuntreated controls serves as a measure of disease control. Pathogen-hostcombinations used were Rhizoctonia solani-cott-on, Pythiumultimum-cotton, Fusarium oxysporum-cucumber. The 3-trichloromethyl-S-chloro-l,2,4-thiadiazole produced 67 percent control of the Pythiumdisease of cotton at 50 parts per million of this compound in the soil.

The herbicidal activity was determined by the greenhouse method 'of Shawand Swanson (Weeds, 1:352-365, 1952). As a post-emergent application ata rate of 16 pounds per acre, the 3-trichloromethyl-5-chloro-1, 2, 4-thiadiazole showed 100 percent control of the broad-leafed mustard andalso of ryegrass. It also produced 80 to 100 percent control of pigweed,mustard and quackgrass at a rate of 8 pounds per acre when applied inacetone solution.

As a foliage fungicide, the compounds of this invention were tested bythe standard slide-germination procedure of the American'Phythopathological Society (Phytopathology, 33: 627-632, 1943). The3-trichloromethyl-5- chloro-1,2,4-thiadiazole produced 99 percentinhibition of spore germination of Monilinia fructicola at 12.5 partsper million.

Example II A solution of 805 milligrams (0.035 mole) of sodium in 20milliliters of andhydrous ethanol was added within minutes with stirringto a solution of 8.3 grams (0.035 mole)3-trichloromethyl-5-chloro-1,2,4-thiadiazole in millimiters of ethanol.After an additional 10 minutes the reaction mixture was neutral and itwas then filtered to remove precipitated sodium chloride. Excess ethanolwas evaporated and the residue was vacuum distilled to obtain 7.2 grams(83 percent of the theoretical yield) of 3-trichloromethyl-5-ethoxy-1,2, 4-thiadiazole. It boiled at 945 C. at 1 mm. Hg pressure and had N==1.5355.

Analysis.Cal. for C H CI N OS: C, 24.26; H, 2.05; 01, 42.97; N. 11.32;s, 12.95. Found: c, 24.03; H, 2.05; CI, 43.28; N, 11.29; S. 13.03.

The 3-trichloromethyl-5-ethoxy-1,2,4-thiadiazole was tested as a soilfungicide against Pythium, Fusarium and R-hizoctonia by the method ofReinhart cited in Example I. The experimental results which wereobtained in comparison with other reference soil fungicides are shown inthe following table:

Percent Disease Control Chemical p.p.m.

Pyth- Fusarium Rhizocium tonia 3-triehlor0methyl-5-ethoxy-l,2,4-thiadiaz0le Zinc Omadine (Zinc pyridinethione), U.S. Patent2,809,971

Captan (N-trichloromethyl-mercaptoieycl0-hexene-1,2-di- 100 82carbox-amide) 68 25 11 12. 5 O

Terraclor (Pentachlor- 100 onitrobenzene) These data show theeffectiveness of this compound against a broad spectrum of importantsoil fungi and its outstanding effectiveness against Pythium at such*low concentrations as 6.25 parts per million. This compound has therare and unexpected property of combining exceptional activity againstPythium with satisfactory control of Fusarium and Rhizoctonia.

The 3-trichloromethyl-S-ethoxy-1,2,4-thiadiazole was further testedagainst Scerotium rolfsii attacking Black Valentine bean and comparedwith Zinc Omadine with the following results:

Control of Pythium attacking cotton growing in nonsterilized soil wasshown by mixing 3-trichloromethyl-5- ethoxy-1,2,4-thiazole into the soilwith the following results.

Conc., p.p.m.: Stand, percent 1 54 Infested check 0 Uninfested check 51The stand in the uninfested check was low, but the improvement obtainedby application of this chemical shows that it controlled pythium andalso an unidentified pathogen of cotton present in the uninfested soil.

Tested as a foliage fungicide, by the method stated in Example I, the3-trichloro-methyl-5-ethoxy-1,2,4-thiadiazole in duplicate tests showed75 and 98 percent inhibitition of spore germination of Monilinafrucricola at 200 p.p.m. and complete inhibition at 400 p.p.m.

Further evaluation for the control of foliage disease was conducted bythe method of McCall'an et al. (A greenhouse method of evaluatingfungicides by means of tomato foliage diseases. Contrib. Boyce ThompsonInst. 13; 93-134, 1943). Tomato plants were sprayed with a series ofconcentrations of the chemical in distilled water. After the spraydried, the plants were inoculated with spores of Alternaria solani andheld at conditions favorable for disease to develop. The number ofdisease lesions on the leaves was counted and compared with the numberdeveloping on the untreated control plants. The ratio of these twonumbers is expressed as percent disease reduction. In this test, the3-trichloro-methyl-5-ethoxy- 1,2,4-thiadiazole produced 95 percentdisease reduction from sprays of 250 p.p.m.

This compound was also shown to exhibit nematocidal activity against aspecies of Meloidogyn'e which produces galls or rootknots on the rootsof tomato, squash, etc. In this test, steam-sterilized soil is infestedwith 6 grams of finely chopped galled tomato root-s per gallon of soil.The chemical is then mixed with the soil at rates of 0.1 to 0.5 gram pergallon which are equivalent to field rates of nem-atocides now in use.The treated infested soil is covered and held for one week, after whicha tomato plant and several squash seeds are transplanted into fourreplicate sub-samples. About 4 weeks later, the roots are washed free ofsoil and the effectiveness of the chemical is determined by counting thenumber of galls from treated versus untreated soil. In this test, the3-trichloromethyl- S-ethoxy-1,2,4-thiadiazole produced 63 percentrootknot control at 0.5 gram per gallon, without causing injury tosquash or tomato.

As a post-emergent application tested by the method of Shaw and Swanson,cited in Example 1, this novel compound also produced 60 percent controlof mustard and ryegrass at a rate of 16 lbs. per acre.

Example 111 A solution of sodium methylate prepared by dissolving 3grams (0.13 mole) of sodium in milliliters of methanol was added to 31garms (0.13 mole) of 3-t-richloromethyl-S-chloro-1,2,4-thiadiazole in 35milliliters of methanol. After stirring for five minutes, the mixturewas neutral. It was filtered to remove precipitated sodium chloride andthe methanol was removed from the filtrate under reduced pressure.Addition of 50 milliliters of petroleum ether to the residueprecipitated additional salt which was filtered off. The filtrate wasevaporated under reduced pressure at 50 C. and the residue wasfractionated. The yield of liquid 3-ttrichloromethyl-5-methoxy-l,2,4-thiadiazole was 27 grams (89.5 percent of theory) boilingat 62 C. at 0.2 mm. Hg pressure and having N =1.5502.

Analysis-Cale. for C H Cl N OS: C, 20.57; H, 1.30; CI, 45.55; N, 12.00;S, 13.73. Found: C, 20.45; H, 1.54; Cl, 45.85; N, 12.10; S, 13.52.

Tested as a post-emergence herbicide by the method cited in Example Ithis compound showed 90 percent control of mustard when applied at therate of 20 pounds per As a soil fungicide, this chemical produced 94percent control of Pythium attacking cotton when applied at the rate of50 ppm mixed into the infested soil. In a further dosage-response testagainst the Pythium disease of cotton, the3-trichloromethyl-S-methoxy-1,2,4-thiadiazole exhibited unusually higheffectiveness at low dosages as shown by the following data.

Conc., p.p.m.: Percent control Example IV A solution of soduimn-butylate prepared by dissolving 3 grams (0.13 mole) of sodium inn-butanol was added to 31 grams (0.13 mole) of3-trichloromethyl-5-chloro- 1,2,4-thiadiazole in 30 milliliters ofn-butanol. The sodium chloride which precipitated on standing at 40 C.for minutes was not readily filterable. Mos-t of the nbutanol wasremoved by evaporation in vacuo and 100 milliliters of petroleum etherwas added. The salt was filtered off, the filtrate was stripped ofsolvents and the residue was distilled in vacuo. The yield of3-trich1oromethyl S-n-bu-toxy-l,2,4-thiadiazole was 31 grams (86.5percent of theory) boiling at 93 at 0.2 mm. Hg pressure and having N=1.5222.

Analysis.Calc. for C H Cl N OS: C, 30.50; H, 3.29; Cl, 38.60; N, 10.17;S, 11.63. Found: C, 30.47; H, 3.19; Cl, 38.54; N, 10.01; S, 11.35.

As a post-emergence herbicide, the 3-trichloromethy1-S-n-butoxy-1,2,4-thiadiazole showed 90 percent control of mustard whenapplied at pounds per acre. As a foliage fungicide, this com-poundshowed 82 percent inhibition of spore germination of Monilina fructicolaat a concentration of 100 parts per million and total inhibition at 400p.p.m.

Example V To a solution of 19 grams (0.08 mole) of3-thichloromethyl-S-chloro-l,2,4-thiadiazole in 50 milliliters ofethanol was added at 10 to 15 C. a 10 percent solution of ammonia inethanol. A slow stream of ammonia gas was passed through the solution atC. for two hours. Ethanol was evaporated in vacuo at 80 C. and theresidue was stirred with 100 milliliters of water, filtered and driedover P 0 in vacuo. The 16 grams of product was recrystallized twice frombenzene to obtain 13 grams (74.5

Example VI A solution of 14.6 grams of diethylamine (0.2 mole) in 70milliliters of benzene was added to a solution of 23.8 grams of3-trichloromethyl-5-chloro-1,2,4-thiadiazole (0.1 mole) in 50 ml. ofbenzene. After keeping the reaction mixture for /2 hour at C., theseparated diethylamine hydrochloride was filtered and the filtrate wasevaporated in vacuo. The residual 3-trichloro-methyl-5-diethylamino-l,2,4-thiadiazole was recrystallized from pctroleum ether.Yield, 25.3 g. or 92 percent of theory M.P. 55 C.

Analysis-Cale. for C H Cl N S: C, 30.61; H, 3.67; Cl, 38.74; N, 15.30;S, 11.67. Found: C, 30.43; H, 3.75; CI, 38.78; N, 15.11; S, 11.69.

The 3-trichloromethyl-S-diethylamino-1,2,4-thiadiazole was tested as apost-emergence herbicide at the rate of 16 pounds per acre and showed 60percent control of mustard.

What is claimed is:

1. The method of controlling fungi which comprises contacting said fungiwith a fungicidal amount of a compound having the formula:

in which X is selected from the group consisting of percent of theory)of 3-trichloromethyl-5-amino-1,2,4-

thiadiazole melting at 196 C.

Analysis.Calc. for C H Cl N S: C, 16.49; H, 0.92; Cl, 48.68; N, 19.23;S, 14.67. Found: C, 16.67; H. 1.20; Cl, 48.55; N, 19.31; S, 14.57.

ing 1 to 4 carbons.

2. The method of controlling weeds which comprises contacting said weedswith a herbicidal amount of a compound having the formula:

ClaCC-N in which X is selected from the group consisting of Cl, MH NHR,NR OR and SR where R is alkyl having 1 to 4 carbons.

3. The method of controlling nematodes which comprises contacting saidnernatodes with a nematocidal amount of a compound having the formula:

C1aC-l(])1fi1' N C-X s in which X is selected from the group consistingof Cl, NH NHR, NR OR and SR where R is alkyl having 1 to 4 carbons.

4. The method of claim 1 in which X is Cl.

5. The method of claim 1 in which X is NH 6. The method of claim 2 inwhich X is 'NHC H 7. The method of claim 2 in which X is N(CH 8. Themethod of claim 1 in which X is OC H 9. The method of claim 3 in which Xis SCH References Cited by the Examiner UNITED STATES PATENTS 3,058,99010/ 1962 Harman 7l2.5 X 3,090,721 5/1963 Uhlenbroek et a1. 16733 LEWISGOTTS, Primary Examiner.

JULIAN S. LEVITT, Examiner.

JAMES C. THOMAS, Assistant Examiner.

1. THE METHOD OF CONTROLLING FUNGI WHICH COMPRISES CONTACTING SAID FUNGIWITH A FUNGICIDAL AMOUNT OF A COMPOUND HAVING THE FORMULA: